Tributylphosphine → 4-(4-Chloro-2-fluoroanilino)-7-(2-ethoxycarbonylpyrid-4-yl)methoxy-6-methoxyquinazoline

HRID 1384680Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1384680
N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.[Cl:19][C:20]1[CH:39]=[CH:38][C:23]([NH:24][C:25]2[C:34]3[C:29](=[CH:30][C:31]([OH:37])=[C:32]([O:35][CH3:36])[CH:33]=3)[N:28]=[CH:27][N:26]=2)=[C:22]([F:40])[CH:21]=1.O[CH2:42][C:43]1[CH:48]=[CH:47][N:46]=[C:45]([C:49]([O:51][CH2:52][CH3:53])=[O:50])[CH:44]=1.C(P(CCCC)CCCC)CCC>C(Cl)Cl>[Cl:19][C:20]1[CH:39]=[CH:38][C:23]([NH:24][C:25]2[C:34]3[C:29](=[CH:30][C:31]([O:37][CH2:42][C:43]4[CH:48]=[CH:47][N:46]=[C:45]([C:49]([O:51][CH2:52][CH3:53])=[O:50])[CH:44]=4)=[C:32]([O:35][CH3:36])[CH:33]=3)[N:28]=[CH:27][N:26]=2)=[C:22]([F:40])[CH:21]=1

Komponenten

6

Edukt 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 14541449Ethyl 4-(hydroxymethyl)picolinateHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Produkt 1

HCID 226249784-(4-Chloro-2-fluoroanilino)-7-(2-ethoxycarbonylpyrid-4-yl)methoxy-6-methoxyquinazolineAusbeute 60 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

1,1′-(azodicarbonyl)dipiperidine (840 mg, 3 mmol) was added in portions to a mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (315 mg, 1 mmol), ethyl 4-hydroxymethyl-2-pyridinecarboxylate (250 mg, 1.4 mmol), (J. Het. Chem. 1993, 30, 631-635) and tributylphosphine (800 μl, 3 mmol) in methylene chloride (50 ml) at 0° C. The mixture was allowed to warm to ambient temperature over 2 hours, the insolubles were removed by filtration and the filtrate was washed with water and brine, dried (Na2SO4) and the solvent removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (10:0 increasing to 9:1). The purified product was recrystallised from methylene chloride/hexane to give 4-(4-chloro-2-fluoroanilino)-7-(2-ethoxycarbonylpyrid-4-yl)methoxy-6-methoxyquinazoline (285 mg, 60%). m.p. 212-214° C. 1H NMR Spectrum (DMSOd6) 1.30(t, 3H); 3.96(s, 3H); 4.35(q, 2H); 5.45(s, 2H); 7.14(s, 1H); 7.35(dd, 1H); 7.5-7.6(m, 2H); 7.85(s, 1H); 8.15(s, 1H); 8.35(s, 1H); 8.75(d, 1H); 9.55(s, 1H)

Aufarbeitung

  1. customthe insolubles were removed by filtration
  2. washthe filtrate was washed with water and brine
  3. dry with materialdried (Na2SO4)
  4. customthe solvent removed by evaporation
  5. customThe residue was purified by column chromatography
  6. washeluting with methylene chloride/methanol (10:0 increasing to 9:1)
  7. customThe purified product was recrystallised from methylene chloride/hexane

Quellen und Nachweise

ORD-Eintrag
ord-f9c061fcd409411e9333561a2780acd4
Quelldatensatz
uspto-grants-2001_07
Patentnummer
US06258951B1

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